scholarly journals Pregnancy and interferon tau regulate RSAD2 and IFIH1 expression in the ovine uterus

Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 285-295 ◽  
Author(s):  
Gwonhwa Song ◽  
Fuller W Bazer ◽  
Thomas E Spencer
Keyword(s):  
Immune Cells ◽  
Transcriptional Profiling ◽  
Immune Defense ◽  
Type I ◽  
Uterine Receptivity ◽  
Antiviral Protein ◽  
Interferon Tau ◽  
Independent Manner ◽  
Uterine Endometrium ◽  
A Cell

Radical S-adenosyl methionine domain containing 2 (RSAD2) encodes a cytoplasmic antiviral protein induced by interferons (IFN). Interferon-induced with helicase C domain 1 (IFIH1) is a RNA helicase involved in innate immune defense against viruses, growth suppression, and apoptosis. Interferon tau (IFNT), a Type I IFN produced by the peri-implantation ruminant conceptus, acts on the uterine endometrium to signal pregnancy recognition and promote receptivity to implantation. Transcriptional profiling identifiedRSAD2andIFIH1as IFNT regulated genes in the ovine uterine endometrium. This study tested the hypothesis thatRSAD2andIFIH1were induced in the endometrium in a cell type-specific manner by IFNT from the conceptus during early pregnancy. EndometrialRSAD2andIFIH1mRNA increased between days 12 and 16 of pregnancy, but not of the estrous cycle. In pregnant ewes,RSAD2andIFIH1mRNAs increased in endometrial glands, and stroma and immune cells, but not in the luminal epithelium. Neither gene was expressed in the trophectoderm of day 18 or 20 conceptuses. Progesterone (P4) treatment of ovariectomized ewes did not induce expressionRSAD2orIFIH1mRNA in the endometrium; however, intrauterine injections of IFNT induced expression ofRSAD2andIFIH1mRNA in endometria of ewes treated with P4, as well as in ewes treated with P4 and the progesterone receptor antagonist, ZK 136,317. These results indicate that conceptus IFNT induces bothRSAD2andIFIH1in a P4-independent manner in the ovine uterine endometrium. These two IFNT-stimulated genes are proposed to have biological roles in the establishment of uterine receptivity to the conceptus during implantation through induction of an antiviral state and modulation of local immune cells in the endometrium.

scholarly journals Bovine endometrium responds differentially to age-matched short and long conceptuses†

2019 ◽  
Vol 101 (1) ◽  
pp. 26-39 ◽  
Author(s):  
José María Sánchez ◽  
Daniel J Mathew ◽  
Susanta K Behura ◽  
Claudia Passaro ◽  
Gilles Charpigny ◽  
...  
Keyword(s):  
Transcriptional Profiling ◽  
In Vitro Production ◽  
Successful Pregnancy ◽  
Interferon Tau ◽  
Independent Manner ◽  
Short Day ◽  
Long Day ◽  
Gene Ontologies ◽  
Vitro Production

Abstract This study combined in vitro production of bovine blastocysts, multiple embryo transfer techniques, and a conceptus-endometrial explant co-culture system to test the hypothesis that bovine endometrium exposed to long vs. short day 15 conceptuses would exhibit a different transcriptome profile reflective of potential for successful pregnancy establishment. Bovine endometrial explants collected at the late luteal stage of the estrous cycle were cultured in RPMI medium for 6 h with nothing (control), 100 ng/mL recombinant ovine interferon tau (IFNT), a long day 15 conceptus, or a short day 15 conceptus. Transcriptional profiling of the endometrial explants found that exposure of endometrium to IFNT, long conceptuses, or short conceptuses altered (P < 0.05) expression of 491, 498, and 230 transcripts, respectively, compared to the control. Further analysis revealed three categories of differentially expressed genes (DEG): (i) commonly responsive to exposure to IFNT and conceptuses, irrespective of size (n = 223); (ii) commonly responsive to IFNT and long conceptuses only (n = 168); and genes induced by the presence of a conceptus but independent of IFNT (n = 108). Of those 108 genes, 101 were exclusively induced by long conceptuses and functional analysis revealed that regulation of molecular function, magnesium-ion transmembrane transport, and clathrin coat assembly were the principal gene ontologies associated with these DEG. In conclusion, bovine endometrium responds differently to age-matched conceptuses of varying size in both an IFNT-dependent and -independent manner, which may be reflective of the likelihood of successful pregnancy establishment.

scholarly journals Conceptus interferon gamma is essential for pregnancy maintenance in the pig

2021 ◽  
Author(s):  
◽  
Destiny Nicole Johns
Keyword(s):  
Interferon Gamma ◽  
Immune Cells ◽  
Interleukin 1 ◽  
Blastocyst Stage ◽  
Type I ◽  
Loss Of Function ◽  
Uterine Endometrium ◽  
Additional Group ◽  
Conceptus Development ◽  
Ifng Production

Establishment and maintenance of pregnancy in the pig is a complex process that relies on adequate communication between the conceptus and maternal uterine endometrium. During the peri-implantation period, the conceptuses produce and secrete estrogens, interleukin 1 beta 2, prostaglandins and other biological factors into the uterine lumen that change the uterine epithelium to become receptive to the attaching conceptuses as well as promote proper conceptus development. Following elongation, beginning on day 12 of pregnancy, the conceptus is known to secrete two different types of interferons. The pig conceptus secretes both type I (interferon delta, IFND) and type II (interferon gamma, IFNG) interferons during this time. CRISPR/Cas9 gene editing and somatic cell nuclear transfer (SCNT) technologies were used to create an IFNG loss-of-function study in pigs. Blastocyst stage embryos that were IFNG[superscript +/+] or IFNG[superscript -/-] were transferred into recipient gilts and their reproductive tracts were collected on days 15 and 17 of pregnancy. Elongated conceptuses were flushed from recipient gilts on day 15 IFNG[superscript +/+] (4/4) and IFNG[superscript -/-] (4/4) recipient gilts. On day 17 of pregnancy, all IFNG[superscript +/+] recipient gilts (4/4) contained elongated viable conceptuses; however, conceptuses were only recovered from 2 of 8 IFNG[superscript -/-] embryo recipient gilts. In all IFNG[superscript -/-] pregnancies, the conceptuses were thin and fragmented compared to IFNG+/+ conceptuses. Additionally, the reproductive tracts that received IFNG[superscript -/-] conceptuses which were not pregnant on day 17 appeared hyperemic, inflamed and edematous. IFNG was localized to the trophectoderm of IFNG[superscript +/+] conceptuses on both day 15 and 17 of pregnancy. However, IFNG expression was not detected in IFNG[superscript -/-] conceptuses on either day 15 or day 17 of pregnancy. Conceptus IFNG mRNA expression was significantly affected by genotype (P [equals] 0.0006) and day (P [less than] 0.0001). Total IFNG was significantly lower (P [equals] 0.0018) in ULF of IFNG[superscript -/-] embryo recipient gilts compared to IFNG[superscript +/+] embryo recipient gilts. IFNG[superscript +/+] conceptuses induced endometrial folding and recruited large numbers of immune cells to the endometrial stroma beneath the site of conceptus attachment compared to less endometrial folding and presence of immune cells in IFNG[superscript -/-] pregnancies on day 15. An additional group of recipient gilts received either IFNG[superscript +/+] embryos (n [equals] 6) or both IFNG[superscript -/-] and IFNG[superscript +/+] embryos (n [equals] 5) to determine if the presence of IFNG producing conceptuses could rescue the IFNG-/- embryos beyond day 17 of pregnancy. On day 30 of pregnancy, 3/6 of IFNG[superscript +/+] embryo recipient gilts contained 3-4 viable embryos, however, only 1 of 5 IFNG[superscript -/-] and IFNG[superscript +/+] cotransferred recipient gilts maintained pregnancy to day 30. Genotyping indicated that all five (1 healthy, 4 degenerating) embryos were IFNG[superscript +/+]. These results indicate conceptus IFNG production is not essential for early conceptus development, rapid elongation or establishment of pregnancy. However, conceptus IFNG production does appear to be necessary for survival during the period of placental attachment beyond day 15.

scholarly journals The role of CAPG in molecular communication between the embryo and the uterine endometrium: Is its function conserved in species with different implantation strategies?

2020 ◽  
Author(s):  
Haidee Tinning ◽  
Alysha Taylor ◽  
Dapeng Wang ◽  
Bede Constantinides ◽  
Ruth Sutton ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transcriptional Response ◽  
Pcr Analysis ◽  
Uterine Receptivity ◽  
Interferon Tau ◽  
Capping Protein ◽  
Uterine Endometrium ◽  
Endometrial Epithelium ◽  
Extraembryonic Membranes ◽  
Endometrial Epithelial Cells

ABSTRACTDuring the pre-implantation period of pregnancy in eutherian mammals, changes to the uterine endometrium are required (both at the transcriptional and protein level) to facilitate the endometrium becoming receptive to an implanting embryo. We know that the developing conceptus (embryo and extraembryonic membranes) produces proteins during this developmental stage. We hypothesised that this common process in early pregnancy in eutheria may be facilitated by highly conserved conceptus-derived proteins such as macrophage capping protein CAPG. More specifically, we propose that CAPG may share functionality in modifying the transcriptome of the endometrial epithelial cells to facilitate receptivity to implantation in species with different implantation strategies, such as human and bovine. A recombinant bovine form of CAPG (91% sequence identity between bovine and human) was produced and bovine endometrial epithelial (bEECs) and stromal (bESCs) cells and human endometrial epithelial cells (hEECs) were cultured for 24 h with or without rbCAPG. RNA sequencing and quantitative real-time PCR analysis was used to assess the transcriptional response to rbCAPG (Control, vehicle, CAPG 10, 100, 1000 ng/ml: n=3 biological replicates per treatment per species). Treatment of bEECs with CAPG resulted in changes to 1052 transcripts (629 increased and 423 decreased) compared to vehicle controls, including those previously only identified as regulated by interferon-tau, the pregnancy recognition signal in cattle. Treatment of hEECs with bovine CAPG increased expression of transcripts previously known to interact with CAPG in different systems (CAPZB, CAPZA2, ADD1 and ADK) compared with vehicle controls (P<0.05). In conclusion, we have demonstrated that CAPG, a highly conserved protein in eutherian mammals elicits a transcriptional response in the endometrial epithelium in two species with different implantation strategies that may facilitate uterine receptivity.

scholarly journals Interferon-tau and fertility in ruminants

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F33-F43 ◽  
Author(s):  
N Forde ◽  
P Lonergan
Keyword(s):  
Prostaglandin F2α ◽  
Threshold Level ◽  
Type I ◽  
Interferon Tau ◽  
Uterine Endometrium ◽  
Domestic Ruminants ◽  
Oxytocin Receptors ◽  
Pregnancy Recognition ◽  
Maternal Recognition Of Pregnancy ◽  
Primary Agent

Establishment of pregnancy in domestic ruminants includes pregnancy recognition signalling by the conceptus, implantation and placentation. Despite the high fertilisation success rate in ruminants, a significant amount of embryo loss occurs, primarily during early gestation. Interferon-tau (IFNT), a type I interferon that is exclusively secreted by the cells of the trophectoderm of the ruminant conceptus, has been recognised as the primary agent for maternal recognition of pregnancy in ruminants. It produces its antiluteolytic effect on the corpus luteum by inhibiting the expression of oxytocin receptors in the uterine epithelial cells, which prevents pulsatile, luteolytic secretion of prostaglandin F2α by the uterine endometrium. While the importance of IFNT in maternal recognition of pregnancy and prevention of luteolysis in ruminants is unequivocal, important questions, for example, relating to the threshold level of IFNT required for pregnancy maintenance, remain unanswered. This paper reviews data linking IFNT with measures of fertility in ruminants.

scholarly journals Transcriptional control of IFNT expression

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F21-F31 ◽  
Author(s):  
Toshihiko Ezashi ◽  
Kazuhiko Imakawa
Keyword(s):  
Transcription Factor ◽  
Binding Site ◽  
Intracellular Signaling ◽  
Transcriptional Control ◽  
Proximal Region ◽  
Type I ◽  
Interferon Tau ◽  
Specific Expression ◽  
Uterine Endometrium ◽  
Separate Site

Once interferon-tau (IFNT) had been identified as a type I IFN in sheep and cattle and its functions were characterized, numerous studies were conducted to elucidate the transcriptional regulation of this gene family. Transfection studies performed largely with human choriocarcinoma cell lines identified regulatory regions of the IFNT gene that appeared responsible for trophoblast-specific expression. The key finding was the recognition that the transcription factor ETS2 bound to a proximal region within the 5′UTR of a bovine IFNT and acted as a strong transactivator. Soon after other transcription factors were identified as cooperative partners. The ETS2-binding site and the nearby AP1 site enable response to intracellular signaling from maternal uterine factors. The AP1 site also serves as a GATA-binding site in one of the bovine IFNT genes. The homeobox-containing transcription factor, DLX3, augments IFNT expression combinatorially with ETS2. CDX2 has also been identified as transactivator that binds to a separate site upstream of the main ETS2 enhancer site. CDX2 participates in IFNT epigenetic regulation by modifying histone acetylation status of the gene. The IFNT downregulation at the time of the conceptus attachment to the uterine endometrium appears correlated with the increased EOMES expression and the loss of other transcription coactivators. Altogether, the studies of transcriptional control of IFNT have provided mechanistic evidence of the regulatory framework of trophoblast-specific expression and critical expression pattern for maternal recognition of pregnancy.

scholarly journals Baculovirus Induces Type I Interferon Production through Toll-Like Receptor-Dependent and -Independent Pathways in a Cell-Type-Specific Manner

2009 ◽  
Vol 83 (15) ◽  
pp. 7629-7640 ◽  
Author(s):  
Takayuki Abe ◽  
Yuuki Kaname ◽  
Xiaoyu Wen ◽  
Hideki Tani ◽  
Kohji Moriishi ◽  
...  
Keyword(s):  
Immune Cells ◽  
Type I Interferon ◽  
Peritoneal Macrophages ◽  
Type I ◽  
Type I Ifn ◽  
Toll Like Receptor ◽  
A Cell ◽  
Nuclear Polyhedrosis

ABSTRACT Autographa californica nuclear polyhedrosis virus (AcNPV) is a double-stranded-DNA virus that is pathogenic to insects. AcNPV was shown to induce an innate immune response in mammalian immune cells and to confer protection of mice from lethal viral infection. In this study, we have shown that production of type I interferon (IFN) by AcNPV in murine plasmacytoid dendritic cells (pDCs) and non-pDCs, such as peritoneal macrophages and splenic CD11c+ DCs, was mediated by Toll-like receptor (TLR)-dependent and -independent pathways, respectively. IFN regulatory factor 7 (IRF7) was shown to play a crucial role in the production of type I IFN by AcNPV not only in immune cells in vitro but also in vivo. In mouse embryonic fibroblasts (MEFs), AcNPV produced IFN-β and IFN-inducible chemokines through TLR-independent and IRF3-dependent pathways, in contrast to the TLR-dependent and IRF3/IRF7-independent production of proinflammatory cytokines. Although production of IFN-β and IFN-inducible chemokines was severely impaired in IFN promoter-stimulator 1 (IPS-1)-deficient MEFs upon infection with vesicular stomatitis virus, AcNPV produced substantial amounts of the cytokines in IPS-1-deficient MEFs. These results suggest that a novel signaling pathway(s) other than TLR- and IPS-1-dependent pathways participates in the production of type I IFN in response to AcNPV infection.

Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation

2009 ◽  
Vol 39 (2) ◽  
pp. 85-99 ◽  
Author(s):  
M. Carey Satterfield ◽  
Gwonhwa Song ◽  
Kelli J. Kochan ◽  
Penny K. Riggs ◽  
Rebecca M. Simmons ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
Growth And Development ◽  
Regulatory Networks ◽  
Corn Oil ◽  
Differentially Expressed ◽  
Biological Processes ◽  
Interferon Tau ◽  
Uterine Endometrium ◽  
A Cell

Establishment of pregnancy in ruminants requires blastocyst growth to form an elongated conceptus that produces interferon tau, the pregnancy recognition signal, and initiates implantation. Blastocyst growth and development requires secretions from the uterine endometrium. An early increase in circulating concentrations of progesterone (P4) stimulates blastocyst growth and elongation in ruminants. This study utilized sheep as a model to identify candidate genes and regulatory networks in the endometrium that govern preimplantation blastocyst growth and development. Ewes were treated daily with either P4 or corn oil vehicle from day 1.5 after mating to either day 9 or day 12 of pregnancy when endometrium was obtained by hysterectomy. Microarray analyses revealed many differentially expressed genes in the endometria affected by day of pregnancy and early P4 treatment. In situ hybridization analyses revealed that many differentially expressed genes were expressed in a cell-specific manner within the endometrium. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to identify functional groups of genes and biological processes in the endometrium that are associated with growth and development of preimplantation blastocysts. Notably, biological processes affected by day of pregnancy and/or early P4 treatment included lipid biosynthesis and metabolism, angiogenesis, transport, extracellular space, defense and inflammatory response, proteolysis, amino acid transport and metabolism, and hormone metabolism. This transcriptomic data provides novel insights into the biology of endometrial function and preimplantation blastocyst growth and development in sheep.

scholarly journals Modulation of EndMT by Hydrogen Sulfide in the Prevention of Cardiovascular Fibrosis

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 910
Author(s):  
Lara Testai ◽  
Vincenzo Brancaleone ◽  
Lorenzo Flori ◽  
Rosangela Montanaro ◽  
Vincenzo Calderone
Keyword(s):  
Hydrogen Sulfide ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Type I ◽  
Vascular Endothelial ◽  
Independent Manner ◽  
Mesenchymal Transition ◽  
Adult Age ◽  
Cardiovascular Fibrosis

Endothelial mesenchymal transition (EndMT) has been described as a fundamental process during embryogenesis; however, it can occur also in adult age, underlying pathological events, including fibrosis. Indeed, during EndMT, the endothelial cells lose their specific markers, such as vascular endothelial cadherin (VE-cadherin), and acquire a mesenchymal phenotype, expressing specific products, such as α-smooth muscle actin (α-SMA) and type I collagen; moreover, the integrity of the endothelium is disrupted, and cells show a migratory, invasive and proliferative phenotype. Several stimuli can trigger this transition, but transforming growth factor (TGF-β1) is considered the most relevant. EndMT can proceed in a canonical smad-dependent or non-canonical smad-independent manner and ultimately regulate gene expression of pro-fibrotic machinery. These events lead to endothelial dysfunction and atherosclerosis at the vascular level as well as myocardial hypertrophy and fibrosis. Indeed, EndMT is the mechanism which promotes the progression of cardiovascular disorders following hypertension, diabetes, heart failure and also ageing. In this scenario, hydrogen sulfide (H2S) has been widely described for its preventive properties, but its role in EndMT is poorly investigated. This review is focused on the evaluation of the putative role of H2S in the EndMT process.

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